Reacción #90607

Ecuación de reacción

tert-butyl (5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)carbamate

TMSI

→

NH4OH MeOH

Rendimiento 5.0%

N-((6-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamide

Rendimiento 28.2%

Disolventes

CH2Cl2

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroA reflux condenser was attached
2. 2
   Otrothe reaction was purged with N2
3. 3
   OtroAfter 1 hr the reaction was quenched with MeOH (5 mL)
4. 4
   workup.STIRRINGstirred for 30 minutes
5. 5
   OtroThe clear brown solution was evaporated to dryness under vacuum
6. 6
   Lavadowashed with aq. Na2S2O3
7. 7
   Otroformed
8. 8
   Filtraciónthat was filtered off),
9. 9
   Secadodried (Na2SO4)
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated under vacuum
12. 12
    OtroPurification by silica gel chromatography (Analogix

Procedimiento

To a stirred solution of tert-butyl (5-((6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamido)methyl)-6-methoxy-4-methylpyridin-2-yl)carbamate (0.80 g, 1.467 mmol) in acetonitrile (20 mL) was added dropwise at RT TMSI (0.50 ml, 3.67 mmol). A reflux condenser was attached and the reaction was purged with N2 and heated to 70° C. After stirring for 30 minutes LCMS indicated that the reaction was complete (89% pure with 11% possible iodinated side product as the only other impurity). After 1 hr the reaction was quenched with MeOH (5 mL) and stirred for 30 minutes. The clear brown solution was evaporated to dryness under vacuum, taken up in CH2Cl2, washed with aq. Na2S2O3, (a ppt. formed that was filtered off), dried (Na2SO4), filtered, and concentrated under vacuum. Purification by silica gel chromatography (Analogix, SF25-10 g, 0 to 7% (5% NH4OH/MeOH) in CH2Cl2) gave the product N-((6-amino-4-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxamide (59.6 mg, 0.138 mmol, 9.4% yield) as a white solid. Note: The ppt. that was filtered off during the aq. Na2S2O3 wash was later shown to contain product. This solid was washed with water and dried under vacuum to give additional product as an off-white solid (602 mg, 1.4 mmol, 95%, 100% pure by LCMS). 1H NMR (400 MHz, DMSO-d6) δ=10.59 (br. s., 1H), 8.13 (t, J=4.4 Hz, 1H), 7.76 (d, J=1.5 Hz, 1H), 7.33 (s, 1H), 6.99 (d, J=1.5 Hz, 1H), 5.83 (br. s., 2H), 5.19 (s, 1H), 4.74 (dt, J=6.6, 13.3 Hz, 1H), 4.22 (d, J=4.8 Hz, 2H), 2.14 (s, 3H), 2.11 (s, 3H), 1.39 (d, J=6.6 Hz, 6H). MS(ES)+ m/e 431.1 [M+H]+.

Fuente